Coronavirus Disease 2019 (COVID-19) PDF

Coronavirus disease
2019 (COVID-19)
The right clinical information, right where it's needed
Last updated: Mar 18, 2020

Table of Contents
Summary 3
Basics 4
Definition 4
Epidemiology 4
Aetiology 5
Pathophysiology 6
Classification 7
Prevention 8
Primary prevention 8
Screening 9
Secondary prevention 9
Diagnosis 10
Case history 10
Step-by-step diagnostic approach 10
Risk factors 16
History & examination factors 16
Diagnostic tests 19
Differential diagnosis 22
Diagnostic criteria 24
Treatment 26
Step-by-step treatment approach 26
Treatment details overview 30
Treatment options 31
Emerging 40
Follow up 42
Recommendations 42
Complications 44
Prognosis 45
Guidelines 47
Diagnostic guidelines 47
Treatment guidelines 48
Online resources 52
References 54
Images 66
Disclaimer 68
Summary
◊ The situation is evolving rapidly with global case counts and deaths increasing each day. The World
Health Organization has declared the COVID-19 outbreak a pandemic and rates the global risk
assessment as very high. Community transmission is occurring in many countries, but it is uncertain
how easily the virus spreads between people. Clinical trials and investigations to learn more about
the virus, its origin, and how it affects humans are ongoing.
Coronavirus disease 2019 (COVID-19) Basics
Definition
Coronavirus disease 2019 (COVID-19) is a potentially severe acute respiratory infection caused by severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus was identified as the cause of an
BASICS
outbreak of pneumonia of unknown cause in Wuhan City, Hubei Province, China, in December 2019.[1] The
clinical presentation is that of a respiratory infection with a symptom severity ranging from a mild common
cold-like illness, to a severe viral pneumonia leading to acute respiratory distress syndrome that is potentially
fatal.
The International Committee on Taxonomy of Viruses has confirmed SARS-CoV-2 as the name of the virus
owing to the virus's genetic similarity to the SARS-CoV virus, but taking into account that there may be
differences in disease spectrum and transmission.[2] [3] The World Health Organization has confirmed
COVID-19 (a shortened version of coronavirus disease 2019) as the name of the disease that SARS-CoV-2
infection causes.[4] Prior to this, the virus and/or disease was known by various names including novel
coronavirus (2019-nCoV), 2019-nCoV, or variations on this.
Epidemiology
The World Health Organization (WHO) was informed of 44 cases of pneumonia of unknown microbial
aetiology associated with Wuhan City, Hubei Province, China on 31 December 2019. Most of the patients
in the outbreak reported a link to a large seafood and live animal market (Huanan South China Seafood
Market).[16] The WHO announced that a novel coronavirus had been detected in samples taken from these
patients. Laboratory tests ruled out severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East
respiratory syndrome (MERS)-CoV, influenza, avian influenza, and other common respiratory pathogens.[17]
Since then, the outbreak has escalated rapidly, with the WHO first declaring a public health emergency of
international concern on 30 January 2020 and then formally declaring it a pandemic on 11 March 2020. The
outbreak spread rapidly from a single city in China to the entire country in only 30 days.[15]
Consult the resources below for updated information on daily case counts:
• [WHO: novel coronavirus (COVID-19) situation dashboard]

• [WHO: coronavirus disease (COVID-2019) situation reports]
• [CDC: coronavirus disease 2019 (COVID-19) – cases in US]
• [CDC: locations with confirmed COVID-19 cases, by WHO region]
• [National Health Committee of the People’s Republic of China: outbreak report]

The Chinese Center for Disease Control and Prevention recently published data from the largest case series
to date (72,314 cases from 31 December 2019 to 11 February 2020). The majority of confirmed cases (87%)
were aged 30 to 79 years, 1% were aged 9 years or younger, 1% were aged 10 to 19 years, and 3% were
aged 80 years or older. Approximately 51% of patients were male and 49% were female. Nearly 4% of cases
were in healthcare workers.[15]
In the US, older patients (aged ≥65 years) accounted for 31% of all cases, 45% of hospitalisations, 53% of
intensive care unit admissions, and 80% of deaths, with the highest incidence of severe outcomes in patients
aged ≥85 years.[19]
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Mar 18, 2020.
BMJ Best Practice topics are regularly updated and the most recent version
of the topics can be found on bestpractice.bmj.com . Use of this content is
subject to our disclaimer. © BMJ Publishing Group Ltd 2020. All rights reserved.
Infection in children is being reported much less commonly than among adults, and all cases so far have
been in family clusters or in children who have a history of close contact with an infected patient.[11] [12] In
a case series of 2143 paediatric patients in China, the median age of children was 7 years, and 56.6% of
cases were in boys although this gender difference was not considered significant.[20]
BASICS
Aetiology
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a previously unknown betacoronavirus
that was discovered in bronchoalveolar lavage samples taken from clusters of patients who presented with
pneumonia of unknown cause in Wuhan City, Hubei Province, China, in December 2019.[1]
SARS-CoV-2 belongs to the Sarbecovirus subgenus of the Coronaviridae family, and is the seventh
coronavirus known to infect humans. The virus has been found to be similar to severe acute respiratory
syndrome (SARS)-like coronaviruses from bats, but it is distinct from SARS-CoV and Middle East respiratory
syndrome (MERS)-CoV.[21] [22] The full genome has been determined and published in GenBank.
[GenBank] A preliminary study suggests that there are two major types (or strains) of the SARS-CoV-2
virus in China, designated L and S. The L type was found to be more prevalent during the early stages of
the outbreak in Wuhan City and may be more aggressive (although this is speculative), but its frequency
decreased after early January. The relevance of this finding is unknown at this stage and further research is
required.[23]
[Fig-1]
Coronaviruses are a large family of enveloped RNA viruses, some of which cause illness in people (e.g.,
common cold, SARS, MERS), and others that circulate among mammals (e.g., bats, camels) and birds.
Rarely, animal coronaviruses can spread to humans and subsequently spread between people, as was the
case with SARS and MERS.
A majority of patients in the initial stages of this outbreak reported a link to the Huanan South China Seafood
Market, a live animal or ‘wet’ market, suggesting a zoonotic origin of the virus.[6] [7] [24] While the potential
animal reservoir and intermediary host(s) are unknown at this point, studies suggest they may derive from a
recombinant virus between the bat coronavirus and an origin-unknown coronavirus; however, this is yet to be
confirmed.[21] [22] [25] [26]
Transmission dynamics of the virus are currently unknown and the situation is rapidly evolving. Person-to-
person spread has been confirmed in community and healthcare settings, with local transmission reported
in many countries around the world. An initial assessment of the transmission dynamics in the first 425
confirmed cases found that 55% of cases before 1 January 2020 were linked to the Huanan South China
Seafood Market, whereas only 8.6% of cases after this date were linked to the market. This confirms that
person-to-person spread occurred among close contacts since the middle of December 2019, including
infections in healthcare workers. One study of a family cluster of five patients in Shenzhen who had a history
of travel to Wuhan City (with one other family member who did not travel to Wuhan City) found that person-
to-person spread is possible in both hospital and family settings.[24] Nosocomial transmission in healthcare
workers and patients has been reported in 41% of patients in one case series.[8] Transmission has been
reported in long-term care facilities.[27]
It is uncertain how easily the virus spreads between people, but transmission in chains involving several links
is increasingly recognised. Similar to SARS and MERS, it is thought that human transmission occurs via
respiratory droplets produced when a person sneezes or coughs.[28] The contribution to transmission by the
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Mar 18, 2020.
5
presence of the virus in other body fluids is unknown; however, the virus has been detected in blood, saliva,
tears, and conjunctival secretions, and faecal transmission may also be possible.[29] [30] [31] [32]
There is mounting evidence that spread from asymptomatic carriers can occur and this has been observed in
BASICS
endemic areas.[33] [34] [35] [36] [37]
Multiple superspreading events have been reported with COVID-19. These events are associated with
explosive growth early in an outbreak and sustained transmission in later stages.[38] Superspreaders can
pass the infection on to large numbers of contacts, including healthcare workers. This phenomenon is well
documented for infections such as severe acute respiratory syndrome (SARS), Ebola virus infection, and
MERS.[39] [40] Some of these individuals are also supershedders of virus, but the reasons underlying
superspreader events are often more complex than just excess virus shedding and can include a variety of
behavioural and environmental factors.[39]
It is unknown whether perinatal transmission or transmission via breastfeeding is possible; however perinatal
transmission has been suspected in one case.[41] [42] Retrospective reviews of pregnant women with
COVID-19 found that there is no evidence for intrauterine infection caused by vertical transmission in women
who develop the infection late in pregnancy. However, there is currently a lack of data about the risk of
transmission to the newborn during vaginal delivery.[43] [44] [45]
Pathophysiology
Current estimates of the incubation period range from 1 to 14 days, according to the World Health
Organization and the US Centers for Disease Control and Prevention.[46] [47] The median incubation period
has been estimated to be approximately 5 days.[24] [48] Transmission may be possible during the incubation
period.[49]
Preliminary reports suggest that the reproductive number (R₀), the number of people who acquire the
infection from an infected person, is approximately 2.2.[24] [50] However, as the situation is still evolving, the
R₀ may actually be higher or lower. The secondary attack rate for SARS-CoV-2 is estimated to be 0.45% for
close contacts of US patients.[51]
While the pathophysiology of this condition is currently unknown, it is thought that the virus binds to
the angiotensin-converting enzyme-2 (ACE2) receptor in humans, which suggests that it may have a
similar pathogenesis to SARS.[22] [52] However, a unique structural feature of the spike glycoprotein
receptor binding domain of SARS-CoV-2 (which is responsible for the entry of the virus into host cells)
confers potentially higher binding affinity for ACE2 on host cells compared to SARS-CoV.[53] A furin-like
cleavage site has been identified in the spike protein of the virus; this does not exist in other SARS-like
coronaviruses.[54]
Based on an analysis of single-cell RNA sequencing datasets derived from major human physiological
systems, the organs considered more vulnerable to SARS-CoV-2 infection due to their ACE2 expression
levels include the lungs, heart, oesophagus, kidneys, bladder, and ileum.[55]
High viral loads have been detected in nasal and throat swabs soon after symptom onset, and it is thought
that the viral shedding pattern may be similar to that of patients with influenza. An asymptomatic patient
was found to have a similar viral load compared with symptomatic patients.[56] The median duration of viral
shedding is approximately 20 days in survivors.[57]
Classification
World Health Organization: clinical classification of COVID-19[5]
BASICS
Mild illness
• Patients with uncomplicated upper respiratory tract viral infection may have non-specific symptoms
such as fever, fatigue, cough (with or without sputum production), anorexia, malaise, muscle pain, sore
throat, dyspnoea, nasal congestion, or headache. Rarely, patients may also present with diarrhoea,
nausea, and vomiting.
• Older and/or immunosuppressed patients may present with atypical symptoms.
• Symptoms due to physiological adaptations of pregnancy or adverse pregnancy events (e.g.,
dyspnoea, fever, gastrointestinal symptoms, fatigue) may overlap with COVID-19 symptoms.
Pneumonia
• Adults: pneumonia with no signs of severe pneumonia (see below) and no need for supplemental
oxygen.
• Children: pneumonia with cough or difficulty breathing plus fast breathing (i.e., <2 months of age: ≥60
breaths/minute; 2-11 months of age: ≥50 breaths/minute; 1-5 years years of age: ≥40 breaths/minute)
and no signs of severe pneumonia (see below).
Severe pneumonia in adults and adolescents
• Fever or suspected respiratory infection plus one of the following:
• Respiratory rate >30 breaths/minute

• Severe respiratory distress
• SpO₂ ≤93% on room air.
Severe pneumonia in children
• Cough or difficulty breathing plus at least one of the following:
• Central cyanosis or SpO₂ <90%

• Severe respiratory distress (e.g., grunting, very severe chest indrawing)
• Signs of pneumonia with a general danger sign (i.e., inability to breastfeed or drink, lethargy or
unconsciousness, or convulsions).
• Other signs of pneumonia may be present in children including chest indrawing or fast breathing (i.e.,
<2 months of age: ≥60 breaths/minute; 2-11 months of age: ≥50 breaths/minute; 1-5 years years of
age: ≥40 breaths/minute).
• While the diagnosis is made on clinical grounds, chest imaging may identify or exclude some
pulmonary complications.
7
Coronavirus disease 2019 (COVID-19) Prevention
Primary prevention
General prevention measures
• The only way to prevent infection is to avoid exposure to the virus and people should be advised to:[60]
[61]
• Wash hands often with soap and water or an alcohol-based hand sanitiser and avoid touching
the eyes, nose, and mouth with unwashed hands
• Avoid close contact with people (i.e., maintain a distance of at least 1 metre [3 feet]), particularly
those who have a fever or are coughing or sneezing
• Practice respiratory hygiene (i.e., cover mouth and nose when coughing or sneezing, discard
tissue immediately in a closed bin, and wash hands)
• Seek medical care early if they have a fever, cough, and difficulty breathing, and share their
previous travel and contact history with their healthcare provider
PREVENTION
• Avoid direct unprotected contact with live animals and surfaces in contact with live animals when
visiting live markets in affected areas
• Avoid the consumption of raw or undercooked animal products, and handle raw meat, milk, or
animal organs with care as per usual good food safety practices.
• [WHO: coronavirus disease (COVID-19) advice for the public]

Medical masks
• The World Health Organization (WHO) does not recommend that people wear a medical mask in
community settings if they do not have respiratory symptoms as there is no evidence available on
its usefulness to protect people who are not ill. However, masks may be worn in some countries
according to local cultural habits. Individuals with fever and/or respiratory symptoms are advised to
wear a mask, particularly in endemic areas.[62]
• It is mandatory to wear a medical mask in public in certain areas of China, and local guidance should
be consulted for more information.
• It is important to wash your hands with soap and water (or an alcohol-based sanitiser) prior to putting
on a face mask.[63]
• [BMJ: facemasks for the prevention of infection in healthcare and community settings]
Screening and quarantine
• People travelling from areas with a high risk of infection may be screened using questionnaires about
their travel, contact with ill persons, symptoms of infection, and/or measurement of their temperature.
Combined screening of airline passengers on exit from an affected area and on arrival elsewhere has
been relatively ineffective when used for other infections such as Ebola virus infection, and has been
modelled to miss up to 50% of cases of COVID-19, particularly those with no symptoms during an
incubation period, which may exceed 10 days.[64] Symptom-based screening processes have been
reported to be ineffective in detecting SARS-CoV-2 infection in a small number of patients who were
later found to have evidence of SARS-CoV-2 in a throat swab.[65]
• Enforced quarantine has been used in some countries to isolate easily identifiable cohorts of people at
potential risk of recent exposure (e.g., groups evacuated by aeroplane from affected areas, or groups
on cruise ships with infected people on board).[66] The psychosocial effects of enforced quarantine
may have long-lasting repercussions.[67] [68]
Coronavirus disease 2019 (COVID-19) Prevention
Vaccine
• There is currently no vaccine available. Vaccines are in development, but it may take some time before
a vaccine is available.[69] [70] An mRNA vaccine (mRNA-1273) has been shipped to the National
Institute of Allergy and Infectious Diseases for phase 1 clinical trials in the US.[71] The vaccine
includes a short segment of genetic code copied from the virus. The trial started in humans on 16
March 2020. Clinical trials in humans have also started on an experimental adenoviral vector vaccine
in China.[72]
Screening
Management of contacts
People who may have been exposed to individuals with suspected COVID-19 (including healthcare workers)
should be advised to monitor their health for 14 days from the last day of possible contact. A contact is
a person who is involved in any of the following from 2 days before, and up to 14 days after, the onset of
symptoms in the patient:[106]
PREVENTION
• Face-to-face contact with a COVID-19 patient within 1 metre (3 feet) for more than 15 minutes
• Providing direct care for patients with COVID-19 without using proper personal protective equipment
• Staying in the same close environment (e.g., workplace, classroom, household, gathering) as a
COVID-19 patient for any amount of time
• Travelling in close proximity within 1 metre (3 feet) with a COVID-19 patient in any kind of conveyance
• Other situations as indicated by local risk assessments.
If a contact develops symptoms, they should notify the receiving facility, wear a medical mask while travelling
to seek care, avoid taking public transport (e.g., call an ambulance or use a private vehicle), perform
respiratory and hand hygiene, sit as far away from others as possible in transit, and clean any contaminated
surfaces.
Screening of travellers
Exit and entry screening may be recommended in some countries, particularly when repatriating nationals
from affected areas. Travellers returning from affected areas should self-monitor for symptoms for 14 days
and follow local protocols of the receiving country. Some countries may require returning travellers to
enter quarantine. Travellers who develop symptoms are advised to contact their local health care provider,
preferably by phone.[107]
Secondary prevention
Early recognition of new cases is the cornerstone of prevention of transmission. Immediately isolate all
suspected and confirmed cases and implement recommended infection prevention and control procedures
according to local protocols, including standard precautions at all times, and contact, droplet, and airborne
precautions while the patient is symptomatic.[74] COVID-19 is a notifiable disease; report all suspected and
confirmed cases to your local health authorities.
Detailed guidance on infection prevention and control measures are available from the World Health
Organization and the Centers for Disease Control and Prevention:
• [WHO: infection prevention and control during health care when COVID-19 is suspected]
• [CDC: interim infection prevention and control recommendations for patients with suspected or
confirmed coronavirus disease 2019 (COVID-19) in healthcare settings]
9
Coronavirus disease 2019 (COVID-19) Diagnosis
Case history
Case history #1
A 61-year-old man presents to hospital on 3 March 2020 with fever, cough, and difficulty breathing. He
also reports feeling very tired and unwell. He has a history of congestive heart failure, which is controlled
with medication. On examination, his pulse is 120 bpm and his temperature is 38.7°C (101.6°F). Chest x-
ray shows bilateral lung infiltrates. He is admitted to hospital in an isolation room and is started on oxygen,
intravenous fluids, empirical antibiotics, and paracetamol. Later that day, he tests positive for severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on real-time reverse transcriptase polymerase
chain reaction testing. The patient develops respiratory distress 7 days after admission and is started on
mechanical ventilation.
Case history #2
A 30-year-old man presents to his general practitioner on 14 January 2020 with a bad cough. He has
had the cough for 4 days and now feels a little short of breath. He also has a headache and reports that
his muscles ache. On examimation, his pulse is 100 bpm and his temperature is 38.5°C (101.3°F). The
patient reports that he returned from a business trip in mainland China 6 days ago.
Other presentations
Other non-specific mild symptoms may include anorexia, confusion, dizziness, sore throat, rhinorrhoea,
and sputum production. Some patients may present with chest pain or haemoptysis. Gastrointestinal
symptoms such as diarrhoea, nausea, vomiting, and abdominal pain have been reported rarely,
although this may be underestimated.[6] [7] [8] [9] [10] Some patients may be minimally symptomatic or
asymptomatic, especially children.[11] [12] [13] [14]
Approximately 80% of patients present with mild illness, 14% present with severe illness, and 5% present
DIAGNOSIS
with critical illness.[15] Patients with severe illness may have signs and symptoms of viral pneumonia, or
complications including acute distress syndrome, acute cardiac injury, arrhythmias, acute kidney injury,
secondary infection, sepsis, or shock.[6] [7] [8]
Atypical presentations may occur, especially in older patients or patients who are immunosuppressed, as
the full spectrum of clinical illness is yet to be characterised.
Step-by-step diagnostic approach

Early recognition and rapid diagnosis are essential to prevent transmission and provide supportive care
in a timely manner. Have a high index of clinical suspicion for COVID-19 in all patients who present with
fever and/or acute respiratory illness and who report a travel history to an affected area or close contact
with a suspected or confirmed case in the 14 days prior to symptom onset. Evaluation should be performed
according to pneumonia severity indexes and sepsis guidelines (if sepsis is suspected) in all patients with
severe illness.
It is important that general practitioners avoid in-person assessment of patients with suspected COVID-19 in
primary care when possible.[73] Algorithms for dealing with these patients are available:
• [BMJ: covid-19 in primary care (UK)]
Infection prevention and control

Triage all patients on admission and immediately isolate all suspected and confirmed cases in an area
separate from other patients. Suspected patients should be given a mask and kept at least 1 metre (3
feet) from other suspected patients. Implement appropriate infection prevention and control procedures.
Screening questionnaires may be helpful. COVID-19 is a notifiable disease; report all suspected and
The World Health Organization (WHO) recommends the following basic principles:[74]
• Immediately isolate all suspected cases in an area that is separate from other patients
• Implement standard precautions at all times:
• Practice hand and respiratory hygiene
• Offer a medical mask to patients who can tolerate one
• Wear personal protective equipment
• Prevent needlestick and sharps injury
• Practice safe waste management, environmental cleaning, and sterilisation of patient care
equipment and linen
• Implement additional contact and droplet precautions until the patient is asymptomatic:
• Place patients in adequately ventilated single rooms; when single rooms are not available,
DIAGNOSIS
place all suspected cases together in the same ward
• Wear a medical mask, gloves, an appropriate gown, and eye/facial protection (e.g., goggles
or a face shield)
• Use single-use or disposable equipment
• Consider limiting the number of healthcare workers, family members, and visitors in contact
with the patient, ensuring optimal patient care and psychosocial support for the patient
• Consider placing patients in negative pressure rooms, if available
• Implement airborne precautions when performing aerosol-generating procedures
• All specimens collected for laboratory investigations should be regarded as potentially infectious.
It is important to disinfect inanimate surfaces in the surgery or hospital as patients may touch and
contaminate surfaces such as door handles and desktops.[75] The median half-life of the virus is
approximately 1 hour as an aerosol, 4 hours on copper, 24 hours on cardboard, and 72 hours on stainless
steel and plastic, based on initial data.[76]
11
Detailed guidance on infection prevention and control procedures are available from the WHO and the
Centers for Disease Control and Prevention (CDC):
• [CDC: strategies for optimizing the supply of facemasks]
History
Take a detailed history to ascertain the level of risk for COVID-19 and assess the possibility of other
causes. Travel history may be key; it is crucial for timely diagnosis and to prevent further transmission.
The diagnosis should be suspected in patients with fever and/or signs/symptoms of acute respiratory
illness (e.g., cough, dyspnoea) who reside in or have travelled to a country/area or territory reporting local
transmission of COVID-19 or who report close contact with a confirmed or probable case of COVID-19 in
the 14 days prior to symptom onset.[77] [59]
Clinical presentation
The clinical presentation resembles viral pneumonia, and the severity of illness ranges from mild to
severe. Approximately 80% of patients present with mild illness, 14% present with severe illness, and 5%
present with critical illness.[15]
Illness severity is associated with older age and the presence of underlying health conditions.[15]
Older patients and/or those with comorbidities may present with mild symptoms, but have a high risk of
deterioration.[5] The most prevalent comorbidities in patients with COVID-19 are hypertension, diabetes,
cardiovascular disease, and respiratory disease.[78]
The most common symptoms are:[6] [7] [8] [9] [79] [80]
DIAGNOSIS
• Fever
• Cough
• Dyspnoea
• Myalgia
• Fatigue.
Less common symptoms include:
• Anorexia
• Sputum production
• Sore throat
• Confusion
• Dizziness
• Headache
• Rhinorrhoea
• Chest pain
• Haemoptysis
• Diarrhoea
• Nausea/vomiting
• Abdominal pain
• Conjunctival congestion.
Some patients may be minimally symptomatic or asymptomatic. Mild illness is defined as patients with an
uncomplicated upper respiratory tract infection with non-specific symptoms such as fever, cough (with or
without sputum production), fatigue, anorexia, malaise, myalgia, sore throat, dyspnoea, nasal congestion,
or headache. Rarely patients may have gastrointestinal symptoms. The most common diagnosis in
patients with severe COVID-19 is severe pneumonia.[5]
Approximately 90% of patients present with more than one symptom, and 15% of patients present with
fever, cough, and dyspnoea.[7] It appears that fewer patients have prominent upper respiratory tract
or gastrointestinal symptoms compared with severe acute respiratory syndrome (SARS), Middle East
respiratory syndrome (MERS), or influenza.[6] [7] Patients may present with nausea or diarrhoea 1 to 2
days prior to onset of fever and breathing difficulties.[8]
A retrospective case series of 62 patients in Zhejiang province found that the clinical features were less
severe than those of the primary infected patients from Wuhan City, indicating that second-generation
infection may result in milder infection. This phenomenon was also reported with MERS.[81]
Children
• Children are typically asymptomatic or present with mild symptoms (e.g., brief and rapidly resolving
fever, mild cough, sore throat, congestion, rhinorrhoea).[11] [12] [13] [14] [82] In a case series
DIAGNOSIS
of 2143 paediatric patients in China, over 90% of children were asymptomatic or had a mild or
moderate illness; 16% were asymptomatic and had no radiological evidence of pneumonia.[20]
However, it is important to note that children may have signs of pneumonia on chest imaging
despite having minimal or no symptoms.[83]
• There is one case report of an infant who had mainly gastrointestinal symptoms.[84]
• Moderate to severe illness has been reported in children.[85]
• Co-infections may be more common in children.[83]
Pregnant women
• Retrospective reviews of pregnant women with COVID-19 found that the clinical characteristics in
pregnant women were similar to those reported for non-pregnant adults.[44]
• It is important to note that symptoms such as fever, dyspnoea, and fatigue may overlap with
symptoms due to physiological adaptations of pregnancy or adverse pregnancy events.[5]
Perform a physical examination. Patients may be febrile (with or without chills/rigors) and have obvious
cough and/or difficulty breathing. Auscultation of the chest may reveal inspiratory crackles, rales, and/or
bronchial breathing in patients with pneumonia or respiratory distress. Patients with respiratory distress
may have tachycardia, tachypnoea, or cyanosis accompanying hypoxia.
13
Initial investigations
Order the following investigations in all patients with severe illness:
• Pulse oximetry
• ABG (as indicated to detect hypercarbia or acidosis)
• FBC
• Comprehensive metabolic panel
• Coagulation screen
• Inflammatory markers (serum procalcitonin and C-reactive protein)
• Serum troponin
• Serum lactate dehydrogenase
• Serum creatine kinase.

The most common laboratory abnormalities in patients hospitalised with pneumonia include leukopenia,
lymphopenia, leukocytosis, elevated liver transaminases, elevated lactate dehydrogenase, and elevated
C-reactive protein. Other abnormalities include neutrophilia, thrombocytopenia, decreased haemoglobin,
decreased albumin, and renal impairment.[6] [7] [8] [80] [86]
Pulse oximetry may reveal low oxygen saturation (SpO₂ <90%).
[VIDEO: Radial artery puncture animated demonstration ]
Blood and sputum cultures

Collect blood and sputum specimens for culture in all patients to rule out other causes of lower respiratory
tract infection and sepsis, especially patients with an atypical epidemiological history. Specimens should
be collected prior to starting empirical antimicrobials if possible.[5]
DIAGNOSIS
Molecular testing
Molecular testing is required to confirm the diagnosis. Diagnostic tests should be performed according
to guidance issued by local health authorities and should adhere to appropriate biosafety practices. If
testing is not available nationally, specimens should be shipped to an appropriate reference laboratory.
Specimens for testing should be collected under appropriate infection prevention and control procedures.
The CDC recommends that the following people are prioritised for testing:[87]
• Hospitalised patients with signs and symptoms of COVID-19

• Other symptomatic people aged 65 years and older and/or those with a chronic medical condition
or who are immunocompromised
• Symptomatic people who have had close contact with a suspected or confirmed case, or have a
history of travel from an affected geographical area, within 14 days of symptom onset.
Symptomatic pregnant women should also be prioritised in order to enable access to specialised care.[5]
Perform a nucleic acid amplification test, such as real-time reverse-transcription polymerase chain
reaction (RT-PCR), for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in all patients with
suspected infection, with confirmation by nucleic acid sequencing when necessary.[88]
• Collect upper respiratory specimens (nasopharyngeal and oropharyngeal swab or wash) in

ambulatory patients and/or lower respiratory specimens (sputum and/or endotracheal aspirate or
bronchoalveolar lavage) in patients with more severe respiratory disease.
• Also consider collecting additional clinical specimens (e.g., blood, stool, urine).
One or more negative results do not rule out the possibility of infection. If a negative result is obtained
from a patient with a high index of suspicion for COVID-19, additional specimens should be collected
and tested, especially if only upper respiratory tract specimens were collected initially.[88] Guidelines
recommend that two consecutive negative tests (at least one day apart) are required to exclude
COVID-19; however, there is a case report of a patient who returned two consecutive negative results
and didn’t test positive until 11 days after symptom onset and confirmation of typical chest computed
tomography (CT) findings.[89]
Collect nasopharyngeal swabs for testing to rule out infection with other respiratory pathogens (e.g.,
influenza, atypical pathogens) according to local guidance. It is important to note that co-infections can
occur, and a positive test for a non-COVID-19 pathogen does not rule out COVID-19.[5] [90]
Serological testing is not available as yet, but assays are in development.[91] Serum samples can be
stored to retrospectively define cases when validated serology tests become available.
Imaging
All imaging procedures should be performed according to local infection prevention and control
procedures to prevent transmission.
Chest x-ray
• Order a chest x-ray in all patients with suspected pneumonia. Unilateral lung infiltrates are found in
DIAGNOSIS
25% of patients, and bilateral lung infiltrates are found in 75% of patients.[6] [7] [92]
CT chest
• Consider ordering a CT scan of the chest. Abnormal chest CT findings have been reported in up to
97% of patients in one meta-analysis of 50,466 hospitalised patients.[79] CT is the primary imaging
modality in China.[93]
• CT imaging generally shows bilateral multiple lobular and subsegmental areas of ground-glass
opacity or consolidation in most patients, usually with a peripheral or posterior distribution, mainly
in the lower lobes and less frequently in the right lower lobe. Consolidative opacities superimposed
on ground-glass opacity may be found in a smaller number of cases, usually older patients. Other
atypical features include interlobular or septal thickening (smooth or irregular), thickening of the
adjacent pleura, subpleural involvement, crazy paving pattern, and air bronchograms. Some
patients may rarely present with pleural effusion, pericardial effusion, bronchiectasis, cavitation,
pneumothorax, lymphadenopathy, and round cystic changes. Atypical features appear to be more
common in the later stages of disease, or on disease progression. None of these findings appear
to be specific or diagnostic for COVID-19.[6] [81] [94] Abnormalities can rapidly evolve from focal
unilateral to diffuse bilateral ground-glass opacities that progress to, or co-exist with, consolidations
within 1 to 3 weeks.[95] The greatest severity of CT findings is usually visible around day 10
15
after symptom onset, and imaging signs associated with clinical improvement (e.g., resolution of
consolidative opacities, reduction in number of lesions and involved lobes) usually occur after week
2 of the disease.[94] A small comparative study found that patients with COVID-19 are more likely
to have bilateral involvement with multiple mottling and ground-glass opacity compared with other
types of pneumonia.[96]
• Small nodular ground-glass opacities are the most common finding in children.[97] Consolidation
with surrounding halo signs is a typical finding in children.[83]
• Evidence of viral pneumonia on CT may precede a positive RT-PCR result for SARS-CoV-2 in
some patients.[91] However, CT imaging abnormalities may be present in minimally symptomatic or
asymptomatic patients.[36] [95] Some patients may present with a normal chest finding despite a
positive RT-PCR.[98]
• In a cohort of over 1000 patients in a hyperendemic area in China, chest CT had a higher
sensitivity for diagnosis of COVID-19 compared with initial RT-PCR from swab samples (88%
versus 59%). Improvement of abnormal CT findings also preceded change from RT-PCR positivity
to negativity in this cohort during recovery. The sensitivity of chest CT was 97% in patients who
ultimately had positive RT-PCR results. However, in this setting, 75% of patients with negative RT-
PCR results also had positive chest CT findings. Of these patients, 48% were considered highly
likely cases, while 33% were considered probable cases.[99]
Risk factors
Strong
residence in/travel to affected area 14 days prior to symptom onset
• Diagnosis should be suspected in patients with fever and/or signs/symptoms of lower respiratory
illness (e.g., cough, dyspnoea) who reside in, or have travelled to a country/area or territory reporting
local transmission of COVID-19 in the 14 days prior to symptom onset.[58] [59]
• [WHO: novel coronavirus (COVID-19) situation dashboard]
DIAGNOSIS
• [CDC: locations with confirmed COVID-19 cases, by WHO region]
close contact with infected individual

• Diagnosis should be suspected in patients with fever and/or signs/symptoms of lower respiratory
illness (e.g., cough, dyspnoea) who report close contact with a confirmed or probable case of
COVID-19 in the 14 days prior to symptom onset.[58] [59]
History & examination factors

Key diagnostic factors
fever (common)
• Reported in 83% to 98% of patients in case series.[6] [7] [8] [79] [80] [100] In one case series, 44% of
patients had a fever on presentation, but it developed in 89% of patients after hospitalisation.[9]
• Less common in children.[14]
• Children may not present with fever, or may have a brief and rapidly resolving fever.[11] [82]
• Patients may present with chills/rigors.
• The course of fever is not fully understood yet, but it may be prolonged and intermittent.
cough (common)
• Reported in 57% to 82% of patients in case series.[6] [7] [8] [9] [79] [80] [100]
• Less common in children.[14]
• Cough is usually dry.
dyspnoea (common)
• Reported in 18% to 55% of patients in case series.[6] [7] [8] [9] [80] [100]
• Median time from onset of symptoms to development of dyspnoea is 5 to 8 days.[6] [7] [8]
Other diagnostic factors

fatigue (common)
• Reported in 29% to 69% of patients in case series.[6] [8] [9] [80] [100]
• Patients may also report malaise.
myalgia (common)
anorexia (common)
• Reported in 40% of patients in case series.[8]
sputum production/expectoration (common)

• Reported in 26% to 33% of patients in case series.[6] [8] [9] [100]
sore throat (common)

• Reported in 5% to 17% of patients in case series, and usually presents early in the clinical course.[7]
[8] [9] [100]
• Children may have pharyngeal erythema.[14]
confusion (uncommon)
DIAGNOSIS
• Reported in 9% of patients in case series.[7]
dizziness (uncommon)
• Reported in 9% to 12% of patients in case series.[8] [80]
headache (uncommon)
haemoptysis (uncommon)
rhinorrhoea (uncommon)
chest pain (uncommon)

• May indicate pneumonia.
17
gastrointestinal symptoms (uncommon)
• Nausea, vomiting, and diarrhoea have been reported in 1% to 10% of patients in case series,
although this may be underestimated.[6] [7] [8] [9] [80] [100] One case series reported gastrointestinal
symptoms in nearly 40% of patients.[10]
• Abdominal pain has been reported in 2% of patients in case series.[8]
• Patients may present with nausea or diarrhoea 1 to 2 days prior to onset of fever and breathing
difficulties.[8]
conjunctival congestion (uncommon)

• Reported in <1% of patients in case series.[9]
bronchial breath sounds (uncommon)

• May indicate pneumonia.
tachypnoea (uncommon)
• May be present in patients with acute respiratory distress.
tachycardia (uncommon)
cyanosis (uncommon)
crackles/rales on auscultation (uncommon)

DIAGNOSIS
Diagnostic tests
1st test to order
Test Result
pulse oximetry may show low ox ygen
saturation (SpO₂ <90%)
• Order in patients with severe illness.
• Recommended in patients with respiratory distress and cyanosis.
ABG may show low partial
ox ygen pressure
• Order in patients with severe illness as indicated to detect
hypercarbia or acidosis.
• Recommended in patients with respiratory distress and cyanosis who
have low oxygen saturation (SpO₂ <90%).
FBC leukopenia; lymphopenia;
leukocytosis
• The most common laboratory abnormalities in patients hospitalised
with pneumonia include leukopenia, lymphopenia, and leukocytosis.
Other abnormalities include neutrophilia, thrombocytopenia, and
decreased haemoglobin.[6] [7] [8] [86]
• Thrombocytopenia has been associated with increased risk of severe
disease and mortality and may be useful as a clinical indicator for
monitoring disease progression.[101]
coagulation screen elevated D-dimer;
prolonged prothrombin
• The most common abnormalities are elevated D-dimer and prolonged time
prothrombin time.[6] [7] [8]
• Non-survivors had significantly higher D-dimer levels and longer
prothrombin time and activated partial thromboplastin time compared
with survivors in one study.[102]
comprehensive metabolic panel elevated liver
transaminases;
DIAGNOSIS
decreased albumin; renal
• The most common laboratory abnormalities in patients hospitalised
impairment
with pneumonia include elevated liver transaminases. Other
abnormalities include decreased albumin and renal impairment.[6] [7]
• Liver function abnormalities may be more common in patients with
COVID-19 compared with other types of pneumonia.[96]
serum procalcitonin may be elevated
• May be elevated in patients with secondary bacterial infection.[6] [7]
May be more common in children.[83]
serum C-reactive protein may be elevated
• May be elevated in patients with secondary bacterial infection.[6] [7]
serum lactate dehydrogenase may be elevated
• Elevated lactate dehydrogenase has been reported in 73% to 76%
of patients.[6] [7] May be more common in patients with COVID-19
compared with other types of pneumonia.[96]
• Indicates liver injury or lysis of blood erythrocytes.
19
Test Result
serum creatine kinase may be elevated
• Elevated creatine kinase has been reported in 13% to 33% of
patients.[6] [7]
• Indicates muscle or myocardium injury.
serum troponin level may be elevated
• May be elevated in patients with cardiac injury.[6]
blood and sputum cultures negative for bacterial
infection
• Collect blood and sputum specimens for culture in all patients to
rule out other causes of lower respiratory tract infection and sepsis,
especially patients with an atypical epidemiological history.[5]
• Specimens should be collected prior to starting empirical
antimicrobials if possible.
real-time reverse transcription polymerase chain reaction (RT- positive for severe acute
PCR) respiratory syndrome
coronavirus 2 (SARS-
• Molecular testing is required to confirm the diagnosis. Nucleic acid
CoV-2) viral RNA; may be
sequencing may be required to confirm the diagnosis.[88]
• Collect upper respiratory specimens (nasopharyngeal and positive for influenza A
and B viruses and other
oropharyngeal swab or wash) in ambulatory patients and/or lower
respiratory pathogens
respiratory specimens (sputum and/or endotracheal aspirate or
bronchoalveolar lavage) in patients with more severe respiratory
disease. Also consider collecting additional clinical specimens (e.g.,
blood, stool, urine). Specimens should be collected under appropriate
infection prevention and control procedures.[88]
• If a negative result is obtained from a patient with a high index of
suspicion for COVID-19, additional specimens should be collected
and tested, especially if only upper respiratory tract specimens were
collected initially.[88]
• Many tests are available under the US Food and Drug
Administration’s emergency-use authorisation scheme.[103] Tests
DIAGNOSIS
are available in many laboratories worldwide and testing should

be done according to instructions from local health authorities and
adhere to appropriate biosafety practices. If testing is not available
nationally, specimens should be shipped to an appropriate reference
laboratory.
• Collect nasopharyngeal swabs to rule out influenza and other
respiratory infections according to local guidance. It is important
to note that co-infections can occur, and a positive test for a non-
COVID-19 pathogen does not rule out COVID-19.[5] [90]
chest x-ray unilateral or bilateral lung
infiltrates
• Order in all patients with suspected pneumonia.
• Unilateral lung infiltrates are found in 25% of patients, and bilateral
lung infiltrates are found in 75% of patients.[6] [7] [92]
computed tomography (CT) chest bilateral ground-glass
opacity or consolidation
• Consider a CT scan of the chest. Abnormal chest CT findings have
been reported in up to 97% of patients in one meta-analysis of
50,466 hospitalised patients.[79] CT is the primary imaging modality
in China.[93]
• CT imaging generally shows bilateral multiple lobular and
subsegmental areas of ground-glass opacity or consolidation in
Test Result
most patients, usually with a peripheral or posterior distribution,
mainly in the lower lobes and less frequently in the right lower lobe.
Consolidative opacities superimposed on ground-glass opacity
may be found in a smaller number of cases, usually older patients.
Other atypical features include interlobular or septal thickening
(smooth or irregular), thickening of the adjacent pleura, subpleural
involvement, crazy paving pattern, and air bronchograms. Some
patients may rarely present with pleural effusion, pericardial effusion,
bronchiectasis, cavitation, pneumothorax, lymphadenopathy, and
round cystic changes. Atypical features appear to be more common
in the later stages of disease, or on disease progression. None of
these findings appear to be specific or diagnostic for COVID-19.[6]
[81] [94] Abnormalities can rapidly evolve from focal unilateral to
diffuse bilateral ground-glass opacities that progress to, or co-exist
with, consolidations within 1 to 3 weeks.[95] The greatest severity
of CT findings is usually visible around day 10 after symptom onset,
and imaging signs associated with clinical improvement (e.g.,
resolution of consolidative opacities, reduction in number of lesions
and involved lobes) usually occur after week 2 of the disease.[94] A
small comparative study found that patients with COVID-19 are more
likely to have bilateral involvement with multiple mottling and ground-
glass opacity compared with other types of pneumonia.[96]
• Small nodular ground-glass opacities are the most common finding
in children.[97] Consolidation with surrounding halo signs is a typical
finding in children.[83]
• Evidence of viral pneumonia on CT may precede a positive RT-
PCR result for SARS-CoV-2 in some patients.[91] However, CT
imaging abnormalities may be present in minimally symptomatic or
asymptomatic patients.[36] [95]
• In a cohort of over 1000 patients in a hyperendemic area in China,
chest CT had a higher sensitivity for diagnosis of COVID-19
compared with initial RT-PCR from swab samples (88% versus
59%). Improvement of abnormal CT findings also preceded change
from RT-PCR positivity to negativity in this cohort during recovery.
The sensitivity of chest CT was 97% in patients who ultimately had
DIAGNOSIS
positive RT-PCR results. However, in this setting, 75% of patients
with negative RT-PCR results also had positive chest CT findings. Of
these patients, 48% were considered highly likely cases, while 33%
were considered probable cases.[99]
[Fig-2]
Emerging tests
Test Result
serology positive for SARS-CoV-2
virus antibodies
• Serological testing is not available as yet, but assays are in
development.[91] Serum samples can be stored to retrospectively
define cases when validated serology tests become available.
21
Differential diagnosis
Condition Differentiating signs / Differentiating tests

symptoms
Middle East respiratory • Lack of travel history to • Reverse-transcriptase
syndrome (MERS) mainland China or other polymerase chain reaction
affected areas, or of close (RT-PCR): positive for
contact with an infected MERS-CoV viral RNA.
person in the 14 days prior to
symptom onset.
• Initial reports suggest
that the clinical course of
COVID-19 is less severe
and the case fatality rate is
lower compared with MERS
(approximately 2% to 3%
for COVID-19 versus 37%
for MERS); however, there
are no data to confirm this
and the situation is rapidly
evolving.[104]
• Gastrointestinal symptoms
and upper respiratory tract
symptoms appear to be less
common in COVID-19 based
on early data.[104] [105]
Severe acute respiratory • There have been no cases of • RT-PCR: positive for SARS-
syndrome (SARS) SARS reported since 2004. CoV viral RNA.
• Lack of travel history to
mainland China or other
affected areas, or of close
contact with an infected
DIAGNOSIS
symptom onset.
• Initial reports suggest
that the clinical course of
COVID-19 is less severe
and the case fatality rate is
lower compared with SARS
(approximately 2% to 3%
for COVID-19 versus 10%
for SARS); however, there
are no data to confirm this
and the situation is rapidly
evolving.[104]
• Gastrointestinal symptoms
and upper respiratory tract
symptoms appear to be less
common in COVID-19 based
on early data.[104] [105]
Community-acquired • Lack of travel history to • Blood or sputum culture or

pneumonia mainland China or other molecular testing: positive for
affected areas, or of close causative organism.

symptoms
symptom onset.
• Differentiating COVID-19
from community-acquired
respiratory tract infections is
not possible from signs and
symptoms.
Influenza infection • Lack of travel history to • RT-PCR: positive for

mainland China or other influenza A or B viral RNA.
symptom onset.
respiratory tract infections
is not possible from signs
and symptoms. However,
early reports suggest that
sore throat is less common
in COVID-19.[105]
Common cold • Lack of travel history to • RT-PCR: positive for

mainland China or other causative organism, or
affected areas, or of close negative for SARS-CoV-2
contact with an infected viral RNA.
symptom onset.
DIAGNOSIS
symptoms. However, early
reports suggest that coryza
and sore throat are less
common in COVID-19.[105]
Avian influenza A (H7N9) • May be difficult to • RT-PCR: positive for H7-

virus infection differentiate based on specific viral RNA.
epidemiological history as
avian influenza H7N9 is
endemic in China.
• Close contact with infected
birds (e.g., farmer or visitor
to a live market in endemic
areas), or living in an area
when avian influenza is
endemic.
• Early reports suggest that
in COVID-19.[105]
Avian influenza A (H5N1) • Lack of travel history to • RT-PCR: positive for H5N1
virus infection mainland China or other viral RNA.
23

symptoms
symptom onset.
• Close contact with infected
birds (e.g., farmer or visitor
to a live market in endemic
areas), or living in an area
when avian influenza is
endemic.
• Early reports suggest that
in COVID-19.[105]
Other viral or bacterial • Lack of travel history to • Blood or sputum culture of

respiratory infections mainland China or other molecular testing: positive for
affected areas, or of close causative organism.
symptom onset.
symptoms.
• Adenovirus and
Mycoplasma should be
considered in clusters
of pneumonia patients,
especially in closed settings
such as military camps and
schools.
Pulmonary tuberculosis • Consider diagnosis in • Chest x-ray: fibronodular

DIAGNOSIS
endemic areas, especially opacities in upper lobes with

in patients who are or without cavitation; atypical
immunocompromised. pattern includes opacities
• History of symptoms is in middle or lower lobes,
usually longer. or hilar or paratracheal
• Presence of night sweats lymphadenopathy, and/or
and weight loss may help to pleural effusion.
differentiate. • Sputum acid-fast bacilli
smear and sputum culture:
positive.
• Molecular testing: positive for
Mycoplasma tuberculosis .
Diagnostic criteria
World Health Organization: case definitions for surveillance[59]
Suspect case
• A. Patients with acute respiratory illness (i.e., fever and at least one sign/symptom of respiratory
disease such as cough or shortness of breath) AND with no other aetiology that fully explains the
clinical presentation AND a history of travel to or residence in a country/area or territory reporting local
transmission of COVID-19 disease during the 14 days prior to symptom onset; OR
• B. Patients with any acute respiratory illness AND having been in contact with a confirmed or probable
COVID-19 case in the last 14 days prior to onset of symptoms; OR
• C. Patients with severe acute respiratory infection (i.e., fever and at least one sign/symptom of
respiratory disease such as cough or shortness of breath) AND requiring hospitalisation AND with no
other aetiology that fully explains the clinical presentation.
Probable case
• A suspect case for whom testing is inconclusive.
Confirmed case
• A person with laboratory confirmation of infection, irrespective of signs and symptoms.

[WHO: global surveillance for COVID-19 disease caused by human infection with the novel coronavirus
(COVID-19)]
Centers for Disease Control and Prevention: criteria to guide

evaluation of patients under investigation (PUI) for COVID-19[77]
Clinicians should use their judgement to determine whether a patient has signs and symptoms compatible
with COVID-19 and whether the patient should be tested. Decisions on which patients receive testing should
be based on the local epidemiology of COVID-19, as well as the clinical course of illness.
Most patients with confirmed COVID-19 have developed fever and/or symptoms of acute respiratory illness
(e.g., cough, difficulty breathing). Epidemiological factors that may help guide decisions on whether to test
include: any persons, including healthcare workers, who have had close contact with a laboratory-confirmed
DIAGNOSIS
COVID-19 patient within 14 days of symptom onset, or a history of travel from affected geographical
areas (international areas with sustained/ongoing transmission) within 14 days of symptom onset. [CDC:
coronavirus disease 2019 (COVID-19) – travel]
Clinicians are strongly encouraged to test for other causes of respiratory illness, including infections such as
influenza.
[CDC: evaluating and testing persons for coronavirus disease 2019 (COVID-19)]
25
Coronavirus disease 2019 (COVID-19) Treatment
Step-by-step treatment approach

No specific treatments are known to be effective for COVID-19 yet; therefore, the mainstay of management
is early recognition and optimised supportive care to relieve symptoms and to support organ function in more
severe illness. Patients should be managed in a hospital setting where possible; however, home care may be
suitable for selected patients with mild illness unless there is concern about rapid deterioration or an inability
to promptly return to hospital if necessary.
Infection prevention and control

Immediately isolate all suspected or confirmed cases in an area separate from other patients. Suspected
cases should be given a mask and kept at least 1 metre (3 feet) from other suspected cases. Implement
appropriate infection prevention and control procedures. COVID-19 is a notifiable disease; report all
suspected and confirmed cases to your local health authorities.
Detailed guidance on infection prevention and control procedures are available from the World Health
Organization (WHO) and the US Centers for Disease Control and Prevention (CDC):
• [CDC: strategies for optimizing the supply of facemasks]
The WHO recommends that patients should remain in isolation for 2 weeks after symptoms disappear,
and visitors should not be allowed until the end of this period.[108] Guidance on when to stop isolation
depends on local circumstances and may differ between countries; consult local guidelines.
Severe COVID-19
Promptly admit patients with pneumonia or acute respiratory distress to an appropriate healthcare facility
and start supportive care depending on the clinical presentation. Patients with impending or established
respiratory failure should be admitted to an intensive care unit. Approximately 14% of patients present
with severe illness requiring oxygen therapy, and 5% present with critical illness requiring intensive care
unit treatment.[15] The median time from onset of symptoms to hospital admission is reported to be
approximately 7 days.[6] [8]
Supportive therapies
• Oxygen and airway management: give supplemental oxygen at a rate of 5 L/minute to patients
with severe acute respiratory infection and respiratory distress, hypoxaemia, or shock. Titrate flow
rates to reach a target SpO₂ ≥94% during resuscitation.[5] Use a face mask with a reservoir bag (at
10-15 L/minute) if the patient is in critical condition. Once the patient is stable, the target SpO₂ is
>90% in children and non-pregnant adults, and ≥92% to 95% in pregnant women. Nasal prongs or
a nasal cannula are preferred in young children.[5]
TREATMENT
• Fluids: manage fluids conservatively in adults and children with severe acute respiratory infection
when there is no evidence of shock as aggressive fluid resuscitation may worsen oxygenation.[5]
• Symptom relief: give an antipyretic/analgesic for the relief of fever and pain.[5]
• There have been media reports stating that non-steroidal anti-inflammatory drugs (NSAIDs)
such as ibuprofen could worsen COVID-19.[109] However, there is currently no strong
evidence to support this, and the situation is being monitored closely.
• The European Medicines Agency recommends that you should consider all available
treatment options in patients with COVID-19 according to each drug’s product information
and national treatment guidelines, although it notes that paracetamol is usually the first-line
option in guidelines.[110] NHS UK recommends paracetamol as the drug of choice until
there is more information available.[111]
• The US Food and Drug Administration is investigating the issue and will release guidance
once more information is available. However, it does note that the label of NSAIDs does warn
of the risk of these drugs potentially diminishing the utility of diagnostic signs in detecting
infections.[112]
• Ibuprofen is not recommended in pregnant women, especially in the third trimester, or
children <6 months of age.
• Antimicrobials: start empirical antimicrobials to cover other potential bacterial pathogens that
may cause respiratory infection according to local protocols. Give within 1 hour of initial patient
assessment for patients with suspected sepsis. Choice of empirical antimicrobials should be
based on the clinical diagnosis, and local epidemiology and susceptibility data. Consider treatment
with a neuraminidase inhibitor until influenza is ruled out. De-escalate empirical therapy based
on microbiology results and clinical judgement.[5] Some patients with severe illness may require
continued antimicrobial therapy once COVID-19 has been confirmed depending on the clinical
circumstances.
Monitoring
• Monitor patients closely for signs of clinical deterioration, such as rapidly progressive respiratory
failure and sepsis, and immediately start general supportive care interventions as indicated
(e.g., haemodialysis, vasopressor therapy, fluid resuscitation, ventilation, antimicrobials) as
appropriate.[5]
Mechanical ventilation
• It is important to follow local infection prevention and control procedures to prevent transmission to
healthcare workers.
• Intubation and mechanical ventilation are recommended in patients who are deteriorating and
failing to respond to standard oxygen therapy. Endotracheal intubation should be performed by
an experienced provider using airborne precautions. Young children, or adults who are obese or
pregnant, may desaturate quickly during intubation and therefore require pre-oxygenation with
100% fraction of inspired oxygen (FiO₂) for 5 minutes.[5] Some patients may develop severe
hypoxic respiratory failure, requiring a high fraction of inspired oxygen, and high air flow rates to
match inspiratory flow demand. Patients may also have increased work of breathing, demanding
positive pressure breathing assistance.
TREATMENT
• High-flow nasal oxygen and non-invasive ventilation are recommended in select patients.
Mechanically ventilated patients with acute respiratory distress syndrome should receive a
lung-protective, low tidal volume/low inspiratory pressure ventilation strategy (lower targets are
recommended in children). Those with persistent severe hypoxic failure should be considered
27
for prone ventilation (pregnant women may benefit from being placed in the lateral decubitus
position).[5]
• The risk of treatment failure is high in patients with non-acutely reversible conditions, and there is
also concern about nosocomial transmission with open ventilation systems and suboptimal non-
invasive face mask or nasal pillow seals. More research to define the balance of benefits and risks
to patients and health workers is needed.
• Some patients may require extracorporeal membrane oxygenation (ECMO) according to availability
and expertise.[5]
Tailor the management of critical illness to the patient’s comorbidities (e.g., decide which chronic
therapies should be continued and which therapies should be temporarily stopped, monitor for drug-drug
interactions). The American Heart Association, the American College of Cardiology, the Heart Failure
Society of America, and the European Society of Cardiology Council on Hypertension recommend that
patients with COVID-19 who have underlying hypertension, heart failure, or ischaemic heart disease
should continue taking their ACE inhibitors or angiotensin-II receptor antagonists as there is no evidence
to suggest that these drugs increase the risk of developing severe COVID-19 despite theoretical concerns
of increased expression of ACE2 in these patients.[113] [114]
Implement standard interventions to prevent complications associated with critical

illness.[5] Complications such as acute respiratory distress syndrome (ARDS), sepsis, and septic shock
should be managed according to usual protocols. See our Complications section for more information.
Mild COVID-19
All laboratory-confirmed cases, regardless of severity, should be managed in a healthcare facility where
possible. In situations where this is not possible, patients with mild illness who have risk factors for poor
outcomes (i.e., age >60 years, presence of comorbidities) should be prioritised for hospital admission.
Patients with mild illness and no risk factors can be isolated in non-traditional facilities (e.g., repurposed
hotels or stadiums) or at home. This will depend on guidance from local health authorities and available
resources. Forced quarantine orders are being used in some countries.[106]
Home care can be considered when the patient can be cared for by family members and follow-up
with a healthcare provider or public health personnel is possible. The decision requires careful clinical
judgement and should be informed by an assessment of the patient’s home environment.[106]
Patients and household members should follow appropriate infection prevention and control measures
while the patient is in home care. Detailed guidance is available from the WHO and CDC:
• [WHO: home care for patients with COVID-19 presenting with mild symptoms and management of
their contacts]
• [CDC: interim guidance for implementing home care of people not requiring hospitalization for
coronavirus disease 2019 (COVID-19)]
Advise patients to limit their interaction, and avoid direct contact with their pets and other animals,
especially while they are symptomatic. At this time, there is no evidence that pets and other animals can
TREATMENT
spread COVID-19; however, caution is advised.[115]
Recommend symptomatic therapies such as an antipyretic/analgesic (taking the precautions above

into account), and advise patients to keep hydrated but not to take too much fluid as this can worsen
oxygenation.
Monitor patients closely and advise them to seek medical care if symptoms worsen as mild illness can
rapidly progress to lower respiratory tract disease. Two negative test results (on samples collected at
least 24 hours apart) are required before the patient can be released from home isolation. If testing
is not possible, the patient should remain in isolation for an additional 2 weeks after symptoms
resolve.[106] Guidance on when to stop isolation depends on local circumstances and may differ between
countries; consult local guidelines.
Pregnancy and breast feeding

Pregnant women should be managed by a multidisciplinary team, including obstetric, perinatal, neonatal,
and intensive care specialists, as well as mental health and psychosocial support. There is no evidence to
suggest that pregnant women present with increased risk of severe illness or fetal compromise. Data on
pregnant women with COVID-19 are limited; however, pregnant women can generally be treated with the
same supportive therapies detailed above, taking into account the physiological changes that occur with
pregnancy.[5]
Location of care
• Manage symptomatic pregnant women with confirmed infection in a hospital setting with
appropriate maternal and fetal monitoring; women with severe illness or complications may require
admission to an intensive care unit.[41]
• Isolate and monitor asymptomatic pregnant women with confirmed infection at home, if appropriate,
with ultrasound fetal surveillance every 2 weeks.[41]
Delivery
• Choice of delivery and timing should be individualised based on gestational age, as well as
maternal, fetal, and delivery conditions. Induction of labour and vaginal delivery is preferred in
pregnant women with confirmed COVID-19 infection to avoid unnecessary surgical complications;
however, an emergency caesarean delivery may be required if medically justified (e.g., in patients
with complications such as sepsis or if there is fetal distress).[5] [41]
• Corticosteroid therapy may be considered in women who are at risk of preterm birth from 24 to 37
weeks’ gestation for fetal lung maturation.[5] [41]
Newborns and breastfeeding
• Babies born to mothers with suspected or confirmed infection should be tested after birth.
• The WHO recommends that mothers and infants should remain together when possible, and
breastfeeding should be encouraged while applying appropriate infection prevention and control
measures (e.g., performing hand hygiene before and after contact with the baby, wearing a mask
while breastfeeding).[5] However, the CDC recommends that temporary separation of the mother
and baby should be considered on a case-by-case basis, at least until the mother’s transmission-
based precautions are discontinued. It recommends that mothers who intend to breastfeed
should be encouraged to express their breast milk using a dedicated breast pump and using
appropriate infection prevention and control measures in order to maintain milk supply. Expressed
TREATMENT
milk should be fed to the newborn by a healthy carer.[116] Consult local guidelines for specific
recommendations.
29
Experimental therapies
Drug therapies (e.g., antivirals) are being used in patients with COVID-19; however, unlicensed or
experimental treatments should only be administered in the context of ethically-approved clinical trials.[5]
See the Emerging section for more information about these treatments.
Corticosteroids
Corticosteroids are being used in some patients with COVID-19; however, they have been found to be
ineffective and are not recommended.[6] [117] The WHO (as well as other international pneumonia
guidelines) do not routinely recommend systemic corticosteroids for the treatment of viral pneumonia
or acute respiratory distress syndrome unless they are indicated for another reason.[5] A randomised
controlled trial investigating the use of corticosteroids in patients with COVID-19 is in progress.[118]
Treatment details overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Initial ( summary )
suspected COVID-19
1st infection prevention and control

procedures
plus empirical antimicrobials
adjunct supportive care plus monitoring
Acute ( summary )
confirmed COVID-19
mild illness with risk 1st hospital admission and infection

factors; severe illness prevention and control procedures
adjunct mechanical ventilation
adjunct experimental therapies
mild illness with no risk 1st isolation in non-traditional facility or at

factors home
plus supportive care plus monitoring

TREATMENT
Treatment options
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
TREATMENT
31
Initial
suspected COVID-19
1st infection prevention and control

procedures
» Immediately isolate all suspected cases in

an area separate from other patients, and
implement appropriate infection prevention and
control procedures. Suspected cases should be
given a mask and kept at least 1 metre (3 feet)
from other suspected cases. Detailed guidance
is available from the World Health Organization
(WHO) and the Centers for Disease Control and
Prevention (CDC):
» [WHO: infection prevention and control during

health care when COVID-19 is suspected]
» [CDC: interim infection prevention and control

recommendations for patients with suspected or
confirmed coronavirus disease 2019 (COVID-19)
in healthcare settings]
» COVID-19 is a notifiable disease; report all

suspected cases to your local health authorities.
plus empirical antimicrobials
Treatment recommended for ALL patients in
selected patient group
» Start empirical antimicrobials to cover other
potential bacterial pathogens that may cause
respiratory infection according to local protocols.
Give within 1 hour of initial patient assessment
for patients with suspected sepsis. Choice of
empirical antimicrobials should be based on the
clinical diagnosis, and local epidemiology and
susceptibility data.[5]
» Consider treatment with a neuraminidase

inhibitor until influenza is ruled out.[5]
» De-escalate empiric therapy based on

microbiology results and clinical judgement.
Treatment recommended for SOME patients in
» Immediately start supportive care based on the
clinical presentation if necessary.
» Oxygen and airway management: give

TREATMENT
supplemental oxygen at a rate of 5 L/minute to

patients with severe acute respiratory infection
and respiratory distress, hypoxaemia, or shock.
Titrate flow rates to reach a target SpO₂ ≥94%
during resuscitation. Use a face mask with a
Initial
reservoir bag (at 10-15 L/minute) if the patient is
in critical condition. Once the patient is stable,
the target SpO₂ is >90% in children and non-
pregnant adults, and ≥92% to 95% in pregnant
women. Nasal prongs or a nasal cannula are
preferred in young children.[5]
» Fluids: manage fluids conservatively in adults

and children with severe acute respiratory
infection when there is no evidence of shock
as aggressive fluid resuscitation may worsen
oxygenation.[5]
» Symptom relief: give an antipyretic/analgesic

for the relief of fever and pain.[5] There have
been media reports stating that non-steroidal
anti-inflammatory drugs (NSAIDs) such as
ibuprofen could worsen COVID-19.[109]
However, there is currently no strong evidence
to support this, and the situation is being
monitored closely. The European Medicines
Agency recommends that you should consider
all available treatment options in patients with
COVID-19 according to each drug’s product
information and national treatment guidelines,
although notes that paracetamol is usually the
first-line option in guidelines.[110] NHS UK
recommends paracetamol as the drug of choice
until there is more information available.[111]
The US Food and Drug Administration is
investigating the issue and will release guidance
once more information is available. However, it
does note that the label of NSAIDs does warn
of the risk of these drugs potentially diminishing
the utility of diagnostic signs in detecting
infections.[112] Ibuprofen is not recommended in
pregnant women, especially in the third trimester,
or children <6 months of age.
» Monitor patients closely for signs of clinical

deterioration, such as rapidly progressive
respiratory failure and sepsis, and immediately
start general supportive care interventions as
indicated (e.g., haemodialysis, vasopressor
therapy, fluid resuscitation, ventilation,
antimicrobials) as appropriate.[5]
» Pregnant women should be managed by

a multidisciplinary team, including obstetric,
perinatal, neonatal, and intensive care
specialists, as well as mental health and
psychosocial support.[5] [41]
TREATMENT
33
Acute
confirmed COVID-19
mild illness with risk 1st hospital admission and infection

factors; severe illness prevention and control procedures
» Promptly admit patients with pneumonia or

acute respiratory distress to an appropriate
healthcare facility. Patients with impending
or established respiratory failure should be
admitted to an intensive care unit.[5]
» Patients with mild illness who have risk factors

for poor outcomes (i.e., age >60 years, presence
of comorbidities) should also be prioritised for
hospital admission when possible.[106]
» Symptomatic pregnant women with confirmed

infection should be managed in a hospital setting
with appropriate maternal and fetal monitoring;
women with severe illness or complications may
require admission to an intensive care unit.[41]
» Immediately isolate all confirmed cases in

an area separate from other patients, and
implement appropriate infection prevention
and control procedures. Detailed guidance is
available from the WHO and the CDC:
» [WHO: infection prevention and control during

health care when COVID-19 is suspected]
» [CDC: interim infection prevention and control

recommendations for patients with suspected or
confirmed coronavirus disease 2019 (COVID-19)
in healthcare settings]
» COVID-19 is a notifiable disease; report all

» The WHO recommends that patients should

remain in isolation for 2 weeks after symptoms
disappear, and visitors should not be allowed
until the end of this period.[108] Guidance
on when to stop isolation depends on local
circumstances and may differ between countries;
consult local guidelines.
TREATMENT
» Immediately start supportive care if necessary.
» Oxygen and airway management: give

supplemental oxygen at a rate of 5 L/minute to
patients with severe acute respiratory infection
and respiratory distress, hypoxaemia, or shock.
Acute
Titrate flow rates to reach a target SpO₂ ≥94%
during resuscitation. Use a face mask with a
reservoir bag (at 10-15 L/minute) if the patient is
in critical condition. Once the patient is stable,
the target SpO₂ is >90% in children and non-
pregnant adults, and ≥92% to 95% in pregnant
women. Nasal prongs or a nasal cannula are
preferred in young children.[5]
» Fluids: manage fluids conservatively in adults

and children with severe acute respiratory
infection when there is no evidence of shock
as aggressive fluid resuscitation may worsen
oxygenation.[5]
» Symptom relief: give an antipyretic/analgesic

for the relief of fever and pain.[5] There have
been media reports stating that non-steroidal
anti-inflammatory drugs (NSAIDs) such as
ibuprofen could worsen COVID-19.[109]
» Monitor patients closely for signs of clinical

deterioration, such as rapidly progressive
respiratory failure and sepsis, and immediately
start general supportive care interventions as
indicated (e.g., haemodialysis, vasopressor
therapy, fluid resuscitation, ventilation,
antimicrobials) as appropriate.[5]
» Tailor the management of critical illness to

the patient’s comorbidities (e.g., decide which
chronic therapies should be continued and which
TREATMENT
therapies should be temporarily stopped, monitor

for drug-drug interactions). The American Heart
Association, the American College of Cardiology,
the Heart Failure Society of America, and the
European Society of Cardiology Council on
Hypertension recommend that patients with
35
Acute
COVID-19 who have underlying hypertension,
heart failure, or ischaemic heart disease
should continue taking their ACE inhibitors or
angiotensin-II receptor antagonists as there is no
evidence to suggest that these drugs increase
the risk of developing severe COVID-19 despite
theoretical concerns of increased expression of
ACE2 in these patients.[113] [114]
» Implement standard interventions to prevent

complications associated with critical illness.[5]
» Patients with severe illness may require

continued antimicrobial therapy once COVID-19
has been confirmed depending on the clinical
circumstances.
» Pregnant women should be managed by

a multidisciplinary team, including obstetric,
perinatal, neonatal, and intensive care
specialists, as well as mental health and
psychosocial support.[5] [41]
adjunct mechanical ventilation
» Intubation and mechanical ventilation are
recommended in patients who are deteriorating
and failing to respond to standard oxygen
therapy.[5] Some patients may develop severe
hypoxic respiratory failure, requiring a high
fraction of inspired oxygen, and high air flow
rates to match inspiratory flow demand. Patients
may also have increased work of breathing,
demanding positive pressure breathing
assistance.
» Endotracheal intubation should be performed

by an experienced provider using airborne
precautions. Young children, or adults who are
obese or pregnant, may desaturate quickly
during intubation and therefore require pre-
oxygenation with 100% fraction of inspired
oxygen (FiO₂) for 5 minutes.[5]
» High-flow nasal oxygen and non-invasive

ventilation are recommended in select patients.
Mechanically ventilated patients with acute
respiratory distress syndrome should receive a
lung-protective, low tidal volume/low inspiratory
pressure ventilation strategy (lower targets are
TREATMENT
recommended in children). Those with persistent

severe hypoxic failure should be considered
for prone ventilation (pregnant women may
benefit from being placed in the lateral decubitus
position).[5]
Acute
» The risk of treatment failure is high in patients
with non-acutely reversible conditions, and there
is also concern about nosocomial transmission
with open ventilation systems and suboptimal
non-invasive face mask or nasal pillow seals.
More research to define the balance of benefits
and risks to patients and health workers is
needed.
» Some patients may require extracorporeal

membrane oxygenation (ECMO) according to
availability and expertise.[5]
» It is important to follow local infection

prevention and control procedures to prevent
transmission to healthcare workers.
adjunct experimental therapies
» Consider using experimental drug therapies.
Antivirals and other drugs are being used in
patients with COVID-19; however, unlicensed
or experimental treatments should only be
administered in the context of ethically-approved
clinical trials.[5] See the Emerging section for
more information about these treatments.
mild illness with no risk 1st isolation in non-traditional facility or at
factors home
» Patients with mild illness and no risk factors

(i.e., age >60 years, presence of comorbidities)
can be isolated in non-traditional facilities (e.g.,
repurposed hotels or stadiums) or at home
when management in a healthcare facility is
not possible. This will depend on guidance
from local health authorities and available
resources.[106] Forced quarantine orders are
being used in some countries.
» Home care can be considered when the

patient can be cared for by family members
and follow-up with a healthcare provider or
public health personnel is possible. The decision
requires careful clinical judgement and should
be informed by an assessment of the patient’s
home environment.[106]
» Asymptomatic pregnant women with

confirmed infection can be managed at home, if
appropriate.[41]
TREATMENT
» Patients and household members should

follow appropriate infection prevention and
control measures. Detailed guidance is available
from the WHO and the CDC:
37
Acute
• [WHO: home care for patients with
COVID-19 presenting with mild symptoms
and management of their contacts]
• [CDC: interim guidance for implementing
home care of people not requiring
hospitalization for coronavirus disease
2019 (COVID-19)]
» Advise patients to limit their interaction, and
avoid direct contact with their pets and other
animals, especially while they are symptomatic.
At this time, there is no evidence that pets and
other animals can spread COVID-19; however,
caution is advised.[115]
» Two negative test results (on samples collected

at least 24 hours apart) are required before the
patient can be released from home isolation.
If testing is not possible, the patient should
remain in isolation for an additional 2 weeks after
symptoms resolve.[106] Guidance on when to
stop isolation depends on local circumstances
and may differ between countries; consult local
guidelines.
plus supportive care plus monitoring
Treatment recommended for ALL patients in
» Recommend symptomatic therapies such as
an antipyretic/analgesic, and advise patients to
keep hydrated but not to take too much fluid as
this can worsen oxygenation.[106]
» There have been media reports stating that

non-steroidal anti-inflammatory drugs (NSAIDs)
such as ibuprofen could worsen COVID-19.[109]
TREATMENT

Acute
» Monitor patients closely and advise them to
seek medical care if symptoms worsen as mild
illness can rapidly progress to lower respiratory
tract disease.
» Ultrasound fetal surveillance is recommended

every 2 weeks in pregnant women.[41]
TREATMENT
39
Emerging
Antivirals
Various antivirals (monotherapy and combination therapy) are being trialled in patients with COVID-19 (e.g.,
oseltamivir, lopinavir/ritonavir, darunavir, ganciclovir, favipiravir, baloxavir marboxil, umifenovir, ribavirin,
interferon alfa); however, there are no data to support their use.[6] [7] [8] [119] [120] [121] [122] [123] [124]
[125] [126] [127] Results from one small case series found that evidence of clinical benefit with lopinavir/
ritonavir was equivocal.[128] A randomised controlled trial of approximately 200 patients in China found that
treatment with lopinavir/ritonavir was not beneficial compared with standard care alone (primary outcome
was time to improvement) in hospitalised patients with severe COVID-19.[129] Remdesivir shows in vitro
activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has been used to treat
patients in China, as well as the first patient in the US.[130] [131] Clinical trials with remdesivir have started
in the US and in China.[132] [133] [134]
Chloroquine and hydrox ychloroquine

Chloroquine and hydroxychloroquine are being trialled in some patients with COVID-19.[135] [136] [137]
Chloroquine shows in vitro activity against SARS-CoV-2.[131] [138] An expert consensus guideline in
China recommends chloroquine in mild to severe cases of COVID-19 as it may improve the success rate of
treatment, shorten hospital stay, and improve patient outcome.[139] The US Food and Drug Administration is
currently investigating the use of chloroquine for treating patients with COVID-19.
Intravenous immunoglobulin
Intravenous immunoglobulin is being trialled in some patients with COVID-19; however, there are no data to
support this.[7]
Traditional Chinese Medicine

Traditional Chinese Medicine is being trialled in some patients with COVID-19 (e.g., Xue-Bi-Jing, Shuang-
Huang-Lian, Xin-Guan-2); however, there are no data to support this.[140] [141] [142] These medicines are
commonly used in China to treat COVID-19 patients and are recommended in local guidelines.[143]
Stem cell therapy

Stem cell therapy is being investigated to treat patients with COVID-19 in clinical trials. It is thought that
mesenchymal stem cells can reduce the pathological changes that occur in the lungs, and inhibit the cell-
mediated immune inflammatory response.[144]
Angiotensin-II receptor antagonists

Angiotensin-II receptor antagonists such as losartan are being investigated as a potential treatment because
it is thought that the angiotensin-converting enzyme-2 (ACE2) receptor is the main binding site for the
virus.[145]
Convalescent plasma
Convalescent plasma from patients who have recovered from viral infections has been used as a treatment
in previous virus outbreaks including SARS, avian influenza, and Ebola virus infection.[146] A clinical trial to
determine the safety and efficacy of convalescent plasma in patients with COVID-19 has started in China;
TREATMENT
however, there is no data on its use as yet.[147]
Other drugs
Other drugs that may show promise for the treatment of COVID-19 include teicoplanin and camostat
mesylate.[148] [149] Sarilumab is being trialled in patients with severe COVID-19.[150] Gimsilumab is in
development for the treatment of acute respiratory distress syndrome associated with COVID-19.[151]
TREATMENT
41
Coronavirus disease 2019 (COVID-19) Follow up
Recommendations
Monitoring
FOLLOW UP
Monitor vital signs (i.e., temperature, respiratory rate, heart rate, blood pressure, oxygen saturation)
and perform haematology and biochemistry laboratory testing and ECG as clinically indicated during
admission. Utilise medical early warning scores that facilitate early recognition and escalation of treatment
of deteriorating patients (e.g., National Early Warning Score 2 [NEWS2]) where possible.[5]
Monitor vital signs three to four times daily and fetal heart rate in pregnant women with confirmed
infection who are symptomatic and admitted to hospital. Perform fetal growth ultrasounds and Doppler
assessments to monitor for potential intrauterine growth restriction in pregnant women with confirmed
infection who are asymptomatic.[41]
Perform molecular testing regularly during admission. Two consecutive negative tests (at least 24 hours
apart) are required in a clinically recovered patient before discharge.[5]
Patient instructions
General prevention measures
• Wash hands often with soap and water or an alcohol-based hand sanitiser and avoid touching the
eyes, nose, and mouth with unwashed hands.
• Avoid close contact with people (i.e., maintain a distance of at least 1 metre [3 feet]), particularly
those who are sick.
• Stay at home if sick and isolate yourself from other people.
• Practice respiratory hygiene (i.e., cover mouth and nose when coughing or sneezing, discard tissue
immediately in a closed bin, and wash hands).
• Regularly clean and disinfect frequently touched objects and surfaces.[60] [61]
• [WHO: coronavirus disease (COVID-19) advice for the public]

Travel advice
• Many countries have implemented international travel bans, have issued advice for domestic travel,
and are requesting that citizens travelling abroad should come home immediately if they are able
to. Some countries are restricting entry to foreign nationals who have been to affected areas in the
preceding 14 days, or are enforcing 14-day quarantine periods where the person’s health should be
closely monitored (e.g., twice-daily temperature readings). Consult local guidance for specific travel
restriction recommendations in your country.
• The World Health Organization (WHO) continues to advise against any travel or trade restrictions
to countries experiencing outbreaks (as of 27 February 2020). However, they do recommend that
international travellers who are sick should delay or avoid travel to affected areas, especially older
people or people with underlying health conditions or chronic diseases. Usual precautions (e.g.,
frequent hand hygiene, cough etiquette, keeping a distance of at least 1 metre [3 feet] from people
showing symptoms, food hygiene practices) are important for all travellers. [WHO: coronavirus
disease (COVID-19) travel advice]
• In the US, the Centers for Disease Control and Prevention (CDC) recommends avoiding all non-
essential travel to China (this does not include Hong Kong, Macau, or Taiwan), South Korea,
Malaysia, Iran, most European countries, the UK, and Ireland as these areas have widespread
sustained ongoing transmission. They also recommend that older adults and those with chronic
medical conditions should consider postponing non-essential travel to any global location. Entry
of foreign nationals from China, Iran, most European countries, the UK, and Ireland has been
suspended. [CDC: coronavirus disease 2019 (COVID-19) – travel] The CDC recommends that all
travellers, particularly older and adults and/or those with underlying health issues, defer all cruise
FOLLOW UP
ship travel worldwide.[169] The US Department of State has issued an advisory instructing all
Americans in the US not to travel, and for Americans living abroad to return home if possible or
avoid international travel unless they are prepared to remain abroad for an indefinite period.[170]
Resources
• [WHO: coronavirus disease (COVID-19) outbreak]

• [CDC: coronavirus (COVID-19)]
• [CDC: healthcare professionals – frequently asked questions and answers]
43
Complications
Complications Timeframe Likelihood

FOLLOW UP
acute respiratory distress syndrome (ARDS) short term medium
Reported in 15% to 33% of patients in case series.[6] [7] [8] [79] [100]
Children can quickly progress to ARDS.[20]
Factors that increase the risk of developing ARDS and death include older age, neutrophilia, elevated
lactate dehydrogenase level, and elevated D-dimer level. Treatment with methylprednisolone may be
beneficial and decrease the risk of death in these patients.[162]
acute liver injury short term medium
Reported in 14% to 53% of patients in case series. Occurs more commonly in patients with severe
disease.[163]
acute cardiac injury short term low
Reported in 7% to 13% of patients in case series.[6] [8] [100] Arrhythmias have been reported in 16% of
patients in case series.[8]
Prevalence is high among patients who are severely or critically ill, and these patients have a higher rate of
in-hospital mortality.[164]
Fulminant myocarditis has been reported.[155] Early corticosteroid therapy and immunoglobulin may be

beneficial in these patients.[165]
Infection may have longer-term implications for overall cardiovascular health; however, further research is
required.[166]
secondary infection short term low
Reported in 6% to 10% of patients in case series.[6] [100]
acute respiratory failure short term low
Reported in 8% of patients in case series.[7]
Leading cause of mortality in patients with COVID-19.[155]
Children can quickly progress to respiratory failure.[20]
acute kidney injury short term low
Reported in 3% to 8% of patients in case series.[6] [7] [100]
septic shock short term low
Reported in 4% to 8% of patients in case series.[6] [7] [8] [100]
A systemic inflammatory response syndrome (SIRS) can sometimes accompany viral sepsis. Elevations in
inflammatory chemokines and cytokines have been reported in COVID-19 patients.[6] [167]
disseminated intravascular coagulation short term low
Complications Timeframe Likelihood

Reported in 71% of non-survivors.[102]
FOLLOW UP
pregnancy-related complications short term low
Retrospective reviews of pregnant women with COVID-19 found that women appeared to have fewer
adverse maternal and neonatal complications and outcomes than would be expected for those with severe
acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). Adverse effects on the
newborn including fetal distress, premature labour, respiratory distress, thrombocytopenia, and abnormal
liver function have been reported; however, it is unclear whether these effects are related to maternal
SARS-CoV-2 infection. No maternal or neonatal deaths, stillbirths, or abortions have been reported so
far.[43] [44] [45] [168]
Prognosis
Case fatality rate

The overall global case fatality rate is approximately 4% based on World Health Organization data as of
19 March 2020. The case fatality rate varies between countries. For example, in Italy, the country with the
highest number of cases outside of China, the case fatality rate is 8%. In Iran, the country with the second
highest number of cases outside of China, the case fatality rate is 6.5%.[152] However, it is important to note
that estimated case fatality rates should be treated with extreme caution as the situation is evolving rapidly,
and case fatality rates are often overestimated at the onset of outbreaks owing to increased case detection of
patients with severe disease.[153]
The overall case fatality rate in China has been estimated to be 2.3% (0.9% in patients without comorbidities)
based on a large case series of 72,314 reported cases from 31 December 2019 to 11 February 2020 (mainly
among hospitalised patients).[15]
The overall case fatality rate appears to be less than that reported for severe acute respiratory syndrome
coronavirus (SARS) (10%) and Middle East respiratory syndrome (MERS) (37%).[6] Despite the lower case
fatality rate, COVID-19 has so far resulted in more deaths than both SARS and MERS combined.[154]
Case fatality rate according to age

The majority of deaths in China have been in patients aged 60 years and older and/or those who have pre-
existing underlying health conditions (e.g., hypertension, diabetes, cardiovascular disease). The case fatality
rate was highest among critical cases (49%). It was also higher in patients aged 80 years and older (15%),
males (2.8% versus 1.7% for females), and patients with comorbidities (10.5% for cardiovascular disease,
7.3% for diabetes, 6.3% for chronic respiratory disease, 6% for hypertension, and 5.6% for cancer).[15]
In the US, the case fatality rate was highest among patients aged ≥85 years (10% to 27%), followed by
those aged 65 to 84 years (3% to 11%), 55 to 64 years (1% to 3%), 20 to 54 years (<1%), and ≤19 years (no
deaths). Patients aged ≥65 years accounted for 80% of deaths.[19]
Causes of death
The leading cause of death in patients with COVID-19 is respiratory failure from acute respiratory distress
syndrome.[155]
In one retrospective study of 52 critically ill patients in Wuhan City, 61.5% of patients died by 28 days,
and the median time from admission to the intensive care unit to death was 7 days for patients who didn’t
survive. Non-survivors were more likely to develop acute respiratory distress syndrome and require
45
mechanical ventilation. Non-survivors were older (>65 years of age) and more likely to have chronic medical
illnesses.[156]
Prognostic factors
FOLLOW UP
Factors associated with disease progression and a poorer prognosis in one retrospective analysis of 78
patients in Wuhan City include older age, history of smoking, maximum body temperature on admission,
respiratory failure, significantly decreased serum albumin level, and significantly elevated C-reactive
protein.[157]
Thrombocytopenia has been associated with increased risk of severe disease and mortality and may be
useful as a clinical indicator for monitoring disease progression.[101]
Other factors associated with a poor prognosis include higher Sequential Organ Failure Assessment (SOFA)
score and a D-dimer level >1 microgram/L. Viral shedding continued until death in non-survivors.[57]
Refractory disease
Refractory disease (patients who do not reach obvious clinical and radiological remission within 10 days
after hospitalisation) has been reported in nearly 50% of hospitalised patients in one retrospective single-
centre study of 155 patients in China. Risk factors for refractory disease include older age, male sex, and
the presence of comorbidities. These patients generally require longer hospital stays as their recovery is
slower.[158]
Infectivity of recovered cases

Potential infectivity of recovered cases is still unclear. There have been case reports of patients testing
positive again after being discharged (i.e., after symptom resolution and two consecutive negative test results
two days apart). This suggests that some patients in convalescence may still be contagious.[159] [160]
Disease reactivation
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reactivation has been reported in patients
after hospital discharge. In a retrospective review of 55 patients in China, 9% of patients presented with
SARS-CoV-2 reactivation. The clinical characteristics were similar to those of non-reactivated patients.
Further research is required on these patients.[161]
Coronavirus disease 2019 (COVID-19) Guidelines
Diagnostic guidelines
Europe
COVID-19: guidance for health professionals

Published by: Public Health England Last published: 2020
COVID-19
Published by: European Centre for Disease Prevention and Control Last published: 2020
International
Country & technical guidance - coronavirus disease (COVID-19)

Published by: World Health Organization Last published: 2020
GUIDELINES
Laboratory testing for coronavirus disease 2019 (COVID-19) in suspected
human cases
Global surveillance for COVID-19 disease caused by human infection with the
novel coronavirus (COVID-19)
Infection prevention and control during health care when COVID-19 is

suspected
North America
Information for laboratories

Published by: Centers for Disease Control and Prevention Last published: 2020
Interim infection prevention and control recommendations for patients with

suspected or confirmed coronavirus disease 2019 (COVID-19) in healthcare
set tings
Interim US guidance for risk assessment and public health management

of persons with potential coronavirus disease 2019 (COVID-19) exposures:
geographic risk and contacts of laboratory-confirmed cases
47
Asia
A rapid advice guideline for the diagnosis and treatment of 2019 novel
coronavirus (2019-nCoV) infected pneumonia
Published by: Zhongnan Hospital of Wuhan University Novel Last published: 2020
Coronavirus Management and Research Team; Evidence-Based
Medicine Chapter of China International Exchange and Promotive
Association for Medical and Health Care
Diagnosis and clinical management of severe acute respiratory syndrome

coronavirus 2 (SARS-CoV-2) infection
Published by: Peking Union Medical College Hospital Last published: 2020
Treatment guidelines
GUIDELINES
Europe
COVID-19: guidance for health professionals

Published by: Public Health England Last published: 2020
Coronavirus (covid-19): latest news and resources

Published by: BMJ Last published: 2020
COVID-19
Published by: European Centre for Disease Prevention and Control Last published: 2020
Guideline for the treatment of people with COVID-19 disease

Published by: Italian Society of Infectious and Tropical Diseases Last published: 2020
Recommendations for COVID-19 clinical management

Published by: National Institute for the Infectious Diseases (Italy) Last published: 2020
Recommendations on the clinical management of the COVID-19 infection by

the new coronavirus SARS-CoV2
Published by: Spanish Paediatric Association Last published: 2020
International
Country & technical guidance - coronavirus disease (COVID-19)

Clinical management of severe acute respiratory infection (SARI) when

COVID-19 disease is suspected
Home care for patients with COVID-19 presenting with mild symptoms and
management of their contacts
Advice on the use of masks in the community, during home care and in health
care set tings in the context of the novel coronavirus (2019-nCoV) outbreak
GUIDELINES
ISUOG interim guidance on 2019 novel coronavirus infection during

pregnancy and puerperium: information for healthcare professionals
Published by: International Society of Ultrasound in Obstetrics and Last published: 2020
Gynecology
49
North America
Information for healthcare professionals

Interim clinical guidance for management of patients with confirmed

coronavirus disease (COVID-19)
Interim guidance for implementing home care of people not requiring

hospitalization for coronavirus disease 2019 (COVID-19)
Discontinuation of in-home isolation for immunocompromised persons with

COVID-19 (interim guidance)
GUIDELINES
Discontinuation of home isolation for persons with COVID-19 (interim

guidance)
Interim U.S. guidance for risk assessment and public health management
of healthcare personnel with potential exposure in a healthcare set ting to
patients with coronavirus disease (COVID-19)
Interim considerations for infection prevention and control of coronavirus

disease 2019 (COVID-19) in inpatient obstetric healthcare set tings
Coronavirus disease (COVID-19): outbreak update

Published by: Government of Canada Last published: 2020
Asia
Coronavirus disease
Published by: Chinese Center for Disease Control and Prevention Last published: 2020
Handbook of COVID-19 prevention and treatment

Published by: First Affiliated Hospital, Zhejiang University School of Last published: 2020
Medicine
A rapid advice guideline for the diagnosis and treatment of 2019 novel
coronavirus (2019-nCoV) infected pneumonia
Published by: Zhongnan Hospital of Wuhan University Novel Last published: 2020
Coronavirus Management and Research Team; Evidence-Based
Medicine Chapter of China International Exchange and Promotive
Association for Medical and Health Care
Diagnosis and clinical management of severe acute respiratory syndrome
GUIDELINES
coronavirus 2 (SARS-CoV-2) infection
Published by: Peking Union Medical College Hospital Last published: 2020
Updates on COVID-19 (coronavirus disease 2019) local situation

Published by: Ministry of Health Singapore Last published: 2020
New coronavirus (COVID-19)#

Published by: National Institute of Infectious Diseases Japan Last published: 2020
New coronavirus infection

Published by: Japanese Association for Infectious Diseases Last published: 2020
Chinese expert consensus on the perinatal and neonatal management for the
prevention and control of the 2019 novel coronavirus infection (first edition)
Published by: Working Committee on Perinatal and Neonatal Last published: 2020
Management for the Prevention and Control of the 2019 Novel
Coronavirus Infection
Oceania
Coronavirus disease 2019 (COVID-19)

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51
Coronavirus disease 2019 (COVID-19) Online resources
Online resources
1. WHO: novel coronavirus (COVID-19) situation dashboard (external link)
2. WHO: coronavirus disease (COVID-2019) situation reports (external link)
3. CDC: coronavirus disease 2019 (COVID-19) – cases in US (external link)
4. CDC: locations with confirmed COVID-19 cases, by WHO region (external link)
5. National Health Committee of the People’s Republic of China: outbreak report (external link)
6. GenBank (external link)
7. WHO: coronavirus disease (COVID-19) advice for the public (external link)
8. BMJ: facemasks for the prevention of infection in healthcare and community settings (external link)
9. BMJ: covid-19 in primary care (UK) (external link)
10. WHO: infection prevention and control during health care when COVID-19 is suspected (external link)
11. CDC: interim infection prevention and control recommendations for patients with suspected or
confirmed coronavirus disease 2019 (COVID-19) in healthcare settings (external link)
12. CDC: strategies for optimizing the supply of facemasks (external link)
13. WHO: global surveillance for COVID-19 disease caused by human infection with the novel coronavirus
ONLINE RESOURCES
(COVID-19) (external link)
14. CDC: coronavirus disease 2019 (COVID-19) – travel (external link)
15. CDC: evaluating and testing persons for coronavirus disease 2019 (COVID-19) (external link)
16. WHO: home care for patients with COVID-19 presenting with mild symptoms and management of their
contacts (external link)
17. CDC: interim guidance for implementing home care of people not requiring hospitalization for
coronavirus disease 2019 (COVID-19) (external link)
18. WHO: coronavirus disease (COVID-19) travel advice (external link)
19. WHO: coronavirus disease (COVID-19) outbreak (external link)
20. CDC: coronavirus (COVID-19) (external link)
Coronavirus disease 2019 (COVID-19) Online resources
21. CDC: healthcare professionals – frequently asked questions and answers (external link)
ONLINE RESOURCES
53
Coronavirus disease 2019 (COVID-19) References
Key articles
References
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65
Coronavirus disease 2019 (COVID-19) Images
Images
IMAGES
Figure 1: Illustration revealing ultrastructural morphology exhibited by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) when viewed with electron microscopically
Centers for Disease Control and Prevention
Coronavirus disease 2019 (COVID-19) Images
IMAGES
Figure 2: Transverse CT scans from a 32-year-old man, showing ground-glass opacity and consolidation of
lower lobe of right lung near the pleura on day 1 after symptom onset (top panel), and bilateral ground-glass
opacity and consolidation on day 7 after symptom onset
Xu XW et al. BMJ. 2020;368:m606
67
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Contributors:
// Authors:
Nicholas J. Beeching, MA, BM BCh, FRCP, FRACP, FFTM RCPS (Glasg), FESCMID, DCH, DTM&H
Consultant and Honorary Senior Lecturer in Infectious Diseases
Royal Liverpool University Hospital and Liverpool School of Tropical Medicine, Liverpool, UK
DISCLOSURES: NJB is partially supported by the National Institute of Health Research Health Protection
Unit (NIHR HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public
Health England (PHE), in collaboration with Liverpool School of Tropical Medicine. He is affiliated with
Liverpool School of Tropical Medicine. The views expressed are those of the author and not necessarily
those of the NHS, the NIHR, the Department of Health, or PHE.
Tom E. Fletcher, MBE, PhD, MBChB, MRCP, DTM&H

Senior Clinical Lecturer and Defence Consultant in Infectious Diseases
Royal Liverpool University Hospital and Liverpool School of Tropical Medicine, Liverpool, UK
DISCLOSURES: TEF is a consultant/expert panel member to the World Health Organization, and is funded
by the UK Surgeon General, the NHS, and Liverpool School of Tropical Medicine. TEF is partially supported
by the National Institute of Health Research Health Protection Unit (NIHR HPRU) in Emerging and Zoonotic
Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with
Liverpool School of Tropical Medicine. He is affiliated with Liverpool School of Tropical Medicine. He has
received research grants from the Wellcome Trust, Medical Research Council, and the UK Public Health
Rapid Support Team (UK-PHRST). The views expressed are those of the author and not necessarily those
of the NHS, the NIHR, the Department of Health, or PHE.
Robert Fowler, MDCM, MS (Epi), FRCP(C)

H. Barrie Fairley Professor of Critical Care
University Health Network and Interdepartmental Division of Critical Care Medicine, Director, Clinical
Epidemiology and Health Care Research, Institute of Health Policy, Management and Evaluation, Dalla
Lana School of Public Health, University of Toronto, Chief, Tory Trauma Program, Sunnybrook Hospital,
Toronto, Canada
DISCLOSURES: RF declares that he has no competing interests.
// Peer Reviewers:
William A. Petri, Jr., MD, PhD

Professor
Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA
DISCLOSURES: WAP declares that he has no competing interests.
Xin Zhang, MD, PhD

Attending Physician
The Fifth Medical Center of PLA General Hospital, Clinical Division and Research Center of Infectious
Disease, Beijing, China
DISCLOSURES: XZ declares that he has no competing interests.
Ran Nir-Pa z, MD
Associate Professor in Medicine
Department of Clinical Microbiology and Infectious Diseases, Hadassah Hebrew University Medical Center,
Jerusalem, Israel
DISCLOSURES: RNP has received research grants from US-Israel Binational Science Foundation, Hebrew
University, Rosetrees Trust, and SpeeDx. He is chair of the European Society of Clinical Microbiology and
Infectious Diseases (ESCMID) Study Group for Mycoplasma and Chlamydia Infections (ESGMAC). RNP
is a consultant for and has stocks in eDAS Healthcare. He is also chairperson of the Israeli Society for
Infectious Diseases guidelines committee.

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Coronavirus disease

The right clinical information, right where it's needed

Last updated: Mar 18, 2020

• [WHO: novel coronavirus (COVID-19) situation dashboard]

• [CDC: coronavirus disease 2019 (COVID-19) – cases in US]

• [CDC: locations with confirmed COVID-19 cases, by WHO region]

• [National Health Committee of the People’s Republic of China: outbreak report]

endemic areas.[33] [34] [35] [36] [37]

• Fever or suspected respiratory infection plus one of the following:

• Respiratory rate >30 breaths/minute

Severe pneumonia in children

• Cough or difficulty breathing plus at least one of the following:

• Central cyanosis or SpO₂ <90%

• [WHO: coronavirus disease (COVID-19) advice for the public]

Step-by-step diagnostic approach

• [BMJ: covid-19 in primary care (UK)]

Infection prevention and control

• Implement standard precautions at all times:

• Practice hand and respiratory hygiene

• Offer a medical mask to patients who can tolerate one

• Wear personal protective equipment

• Prevent needlestick and sharps injury

• Use single-use or disposable equipment

• Consider placing patients in negative pressure rooms, if available

• Implement airborne precautions when performing aerosol-generating procedures

• ABG (as indicated to detect hypercarbia or acidosis)

• Comprehensive metabolic panel

• Inflammatory markers (serum procalcitonin and C-reactive protein)

• Serum lactate dehydrogenase

• Serum creatine kinase.

Pulse oximetry may reveal low oxygen saturation (SpO₂ <90%).

[VIDEO: Radial artery puncture animated demonstration ]

Blood and sputum cultures

• Hospitalised patients with signs and symptoms of COVID-19

• Collect upper respiratory specimens (nasopharyngeal and oropharyngeal swab or wash) in

• [CDC: locations with confirmed COVID-19 cases, by WHO region]

close contact with infected individual

History & examination factors

Other diagnostic factors

sputum production/expectoration (common)

sore throat (common)

chest pain (uncommon)

conjunctival congestion (uncommon)

bronchial breath sounds (uncommon)

crackles/rales on auscultation (uncommon)

are available in many laboratories worldwide and testing should

Condition Differentiating signs / Differentiating tests

Community-acquired • Lack of travel history to • Blood or sputum culture or

Condition Differentiating signs / Differentiating tests

Influenza infection • Lack of travel history to • RT-PCR: positive for

Common cold • Lack of travel history to • RT-PCR: positive for

Avian influenza A (H7N9) • May be difficult to • RT-PCR: positive for H7-

Condition Differentiating signs / Differentiating tests

Other viral or bacterial • Lack of travel history to • Blood or sputum culture of

Pulmonary tuberculosis • Consider diagnosis in • Chest x-ray: fibronodular

endemic areas, especially opacities in upper lobes with

• A suspect case for whom testing is inconclusive.

• A person with laboratory confirmation of infection, irrespective of signs and symptoms.

Centers for Disease Control and Prevention: criteria to guide

Step-by-step treatment approach

Infection prevention and control

Implement standard interventions to prevent complications associated with critical

spread COVID-19; however, caution is advised.[115]